Forever chemicals may result in a higher risk of liver disease in adolescents

 A new study co-led by the Southern California Superfund Research and Training Program for PFAS Assessment, Remediation and Prevention (ShARP) Center and the University of Hawai'i has linked certain common "forever chemicals" to a higher risk of liver disease in adolescents.

Perfluoroheptanoic acid (PFHpA)

These synthetic compounds, known as per- and polyfluoroalkyl substances (PFAS), may as much as triple the chances that adolescents develop a liver condition called metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as fatty liver disease.

MASLD affects about 10% of children and up to 40% of children with obesity. It is a chronic condition that doesn't always have tell tale symptoms, although some patients experience fatigue, discomfort and abdominal pain. The disease increases long-term risk for type 2 diabetes, heart disease, advanced liver injury, cirrhosis and even liver cancer.

"MASLD can progress silently for years before causing serious health problems," said Dr Lida Chatzi, a professor of population and public health sciences and pediatrics and the director of the ShARP Center, a national center that investigates PFAS health impacts, advances cleanup technologies and support affected communities. "When liver fat starts accumulating in adolescence, it may set the stage for a lifetime of metabolic and liver health challenges. If we reduce PFAS exposure early, we may help prevent liver disease later. That's a powerful public-health opportunity."

PFAS are manufactured chemicals used in nonstick cookware, stain- and water-repellent fabrics, food packaging and some cleaning products. They persist in the environment and accumulate in the body over time. More than 99% of people in the US have measurable PFAS in their blood, and at least one PFAS is present in roughly half of US drinking water supplies.

"Adolescents are particularly more vulnerable to the health effects of PFAS as it is a critical period of development and growth," said the study's first and corresponding author, Dr Shiwen "Sherlock" Li, an assistant professor of public health sciences at the University of Hawai'i. "In addition to liver disease, PFAS exposure has been associated with a range of adverse health outcomes, including several types of cancer."

The research examined 284 Southern California adolescents and young adults from two USC longitudinal studies. The participants were already at higher metabolic risk because their parents had type 2 diabetes or were overweight. PFAS levels were measured through blood tests, and liver fat was assessed using MRI.

Higher blood levels of two common PFAS - perfluorooctanoic acid (PFOA) and perfluoroheptanoic acid (PFHpA) - were linked to a greater likelihood of MASLD. Adolescents with twice as much PFOA in their blood were nearly three times more likely to have MASLD. The risk was even higher for those with a genetic variant (PNPLA3 GG) known to influence liver fat. In young adults, smoking further amplified PFAS-related liver impacts.

"These findings suggest that PFAS exposures, genetics and lifestyle factors work together to influence who has greater risk of developing MASLD as a function of your life stage," said Dr Max Aung, assistant professor of population and public health sciences at the Keck School of Medicine. "Understanding gene and environment interactions can help advance precision environmental health for MASLD."

Li noted that this study is the first to examine PFAS and MASLD in children using gold-standard diagnostic criteria, and the first to explore how genetic and lifestyle factors may interact with PFAS exposure. MASLD also became more common as adolescents grew older, adding to evidence that puberty and early adulthood may increase susceptibility to environmental exposures.

The study builds on recent USC research showing that, for adolescents undergoing bariatric surgery to manage obesity, a PFAS known as PFHpA is linked to more severe liver disease, including inflammation and scarring of connective tissue called fibrosis.

"Taken together, the two studies show that PFAS exposures not only disrupt liver biology but also translate into real liver disease risk in youth," added Chatzi. "Adolescence seems to be a critical window of susceptibility, suggesting PFAS exposure may matter most when the liver is still developing."

The findings were reported in the paper, ‘Associations between per- and polyfluoroalkyl substances and metabolic dysfunction-associated steatotic liver disease in adolescents and young adults: modifying roles of age, lifestyle factors, and PNPLA3 genotype’, published in Environmental Research. To access this paper, please click here